tbuckley/cabot-search huggingface dataset:
Once-daily roflumilast foam 0.3% for scalp and body psoriasis: a randomized, double-blind, vehicle-controlled phase IIb study
Authors: Leon H Kircik, Javier Alonso-Llamazares, Neal Bhatia, Michael Bukhalo, Alim R Devani, Zoe D Draelos, Janet DuBois, Melinda J Gooderham, Steven E Kempers, Edward  Lain, Mark Lee, Angela Moore, Dedee F Murrell, Kim A Papp, David M Pariser, Rodney  Sinclair, Matthew Zirwas, Patrick Burnett, Robert C Higham, David Krupa, David R Berk
Journal: British Journal of Dermatology (2023)

Scalp psoriasis affects most patients with psoriasis, but it can be difficult to treat.To evaluate the efficacy and safety of once-daily roflumilast foam 0.3% on scalp and body psoriasis.In a phase IIb randomized controlled trial, adults and adolescents aged ≥ 12 years with scalp and body psoriasis were randomized (2 : 1) to roflumilast foam 0.3% or vehicle for 8 weeks. The primary efficacy endpoint was scalp Investigator Global Assessment (S-IGA) success (score of 'clear' or 'almost clear' plus ≥ 2-grade improvement from baseline) at week 8. Safety and tolerability were also evaluated.Significantly more roflumilast-treated patients (59.1%) than vehicle-treated patients (11.4%) achieved S-IGA success at week 8 (P < 0.001); differences favoured roflumilast as early as the first postbaseline visit at week 2 (P < 0.001). Significant improvements were also seen for secondary endpoints, including body IGA success, Scalp Itch Numeric Rating Scale and the Psoriasis Scalp Severity Index. The safety of roflumilast was generally similar to vehicle. Patients treated with roflumilast experienced low rates of treatment-emergent adverse events (AEs), with few discontinuations due to an AE. Few patients with skin of colour (11%) and few adolescents (0.7%) were included.The results support the further development of roflumilast foam for treating scalp and body psoriasis.
Dual targeting PET tracer [<sup>68</sup>Ga]Ga-FAPI-RGD in patients with lung neoplasms: a pilot exploratory study
Authors: Rongxi Wang, Vivianne Jakobsson, Jiarou Wang, Tianzhi Zhao, Xingtong Peng, Bowen Li, Jianchao Xue, Naixin Liang, Zhaohui Zhu, Xiaoyuan Chen, Jingjing Zhang
Journal: Theranostics (2023)

Rationale: Early discovery, accurate diagnosis, and staging of lung cancer is essential for patients to receive appropriate treatment.PET/CT has become increasingly recognized as a valuable imaging modality for these patients, but there remains room for improvement in PET tracers.We aimed to evaluate the feasibility of using [ 68 Ga]Ga-FAPI-RGD, a dual-targeting heterodimeric PET tracer that recognizes both fibroblast activation protein (FAP) and integrin αvβ3 for detecting lung neoplasms, by comparing it with [ 18 F]FDG and single-targeting tracers [ 68 Ga]Ga-RGD and [ 68 Ga]Ga-FAPI.Methods: This was a pilot exploratory study of patients with suspected lung malignancies.All 51 participants underwent [ 68 Ga]Ga-FAPI-RGD PET/CT, of which: 9 participants received dynamic scans, 44 participants also underwent [ 18 F]FDG PET/CT scan within two weeks, 9 participants underwent [ 68 Ga]Ga-FAPI PET/CT scan and 10 participants underwent [ 68 Ga]Ga-RGD PET/CT scan.The final diagnosis was made based on histopathological analyses and clinical follow-up reports.Results: Among those who underwent dynamic scans, the uptake of pulmonary lesions increased over time.The optimal timepoint for a PET/CT scan was identified to be 2 h post-injection.[ 68 Ga]Ga-FAPI-RGD had a higher detection rate of primary lesions than [ 18 F]FDG (91.4% vs. 77.1%,p < 0.05), higher tumor uptake (SUVmax, 6.9 ± 5.3 vs. 5.3 ± 5.4, p < 0.001) and higher tumor-to-background ratio (10.0 ± 8.4 vs. 9.0 ± 9.1, p < 0.05), demonstrated better accuracy in mediastinal lymph node evaluation (99.7% vs. 90.9%,p < 0.001), and identified more metastases (254 vs. 220).There was also a significant difference between the uptake of [ 68 Ga]Ga-FAPI-RGD and [ 68 Ga]Ga-RGD of primary lesions (SUVmax, 5.8 ± 4.4 vs. 2.3 ± 1.3, p < 0.001). Conclusion:In our small scale cohort study, [ 68 Ga]Ga-FAPI-RGD PET/CT gave a higher primary tumor detection rate, higher tracer uptake, and improved detection of metastases compared with [ 18 F]FDG PET/CT, and [ 68 Ga]Ga-FAPI-RGD also had advantages over [ 68 Ga]Ga-RGD and was non-inferior to [ 68 Ga]Ga-FAPI.We thus provide proof-of-concept for using [ 68 Ga]Ga-FAPI-RGD PET/CT for diagnosing lung cancer.With the stated advantages, the dual-targeting FAPI-RGD should also be explored for therapeutic use in future studies.
Financial outcomes of adolescent and young adult cancer survivors: a longitudinal population-based registry study
Authors: Ties M Siebinga, Silvie H M Janssen, Anke W Boumans, Mies C Van Eenbergen, Bettina Siflinger, Winette T A Van Der Graaf, Olga Husson
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background The patterns and determinants of long-term income among adolescent and young adult (AYA) cancer survivors, and the differences compared with peers, have not yet been fully explored. This study investigated the long-term effects of cancer on the income of AYA cancer survivors. Methods The Netherlands Cancer Registry identified all AYA cancer patients (aged 18-39 years) diagnosed in 2013 and alive 5 years postdiagnosis. Clinical data of the selected AYA patients were linked to individual, administrative real-world labor market data of Statistics Netherlands. The control group consisted of a random sample of individuals of the same age, sex, and migration background without cancer. Data on 2434 AYA cancer patients and 9736 controls were collected annually from 2011 until 2019. Changes in income level were measured and compared with the control group using difference-in-difference regression models. Results AYA cancer survivors experience, on average, an 8.5% decrease in annual earnings, relative to the control population. The effects are statistically significant and permanent (P &amp;lt; .01). Younger AYAs (those aged 18-25 years 15.5% income reduction), married cancer survivors (12.3%), females (11.6%), those diagnosed with stage IV disease (38.1%), and central nervous system (15.7%) cancer patients experienced the largest decline in income, on average, relative to controls, all else constant. Conclusion Although dependent on the sociodemographic and clinical characteristics, a cancer diagnosis at AYA age has significant implications on the income of cancer patients. Awareness of vulnerable groups and the development of policies to mitigate the financial impact of cancer are critical.
Weakened by a decade of austerity: why the UK’s covid-19 inquiry is right to look at policies since 2010
Authors: Martin McKee, Lucinda Hiam, Danny Dorling
Journal: BMJ (2023)

Any concerns that the UK's covid-19 inquiry would give ministers an easy ride seem to have been dispelled by the determination with which its chair, Heather Hallett, has pursued information held by former prime minister Boris Johnson. 1 The government, likely alarmed by the risk of disclosing similar information from current ministers, fought back with a judicial review of her action. 2Inevitably, this unprecedented measure has dominated media coverage, diverting attention from an equally important development: reports that the inquiry will take evidence from former prime minister, David Cameron, and former chancellor of the exchequer, George Osborne. 3 Given the pandemic began in 2020 and both men had left office four years previously, some may ask what interest their testimony can be to the inquiry.In fact, the decision to invite them sends out a very important message.Much attention has, rightly, focused on the events during the first few weeks of the pandemic.The release of the questions sent by Heather Hallett to Boris Johnson, a consequence of the government's legal action, has revealed her interest in why the then prime minister seemed so disengaged from what was happening, and in particular why he failed to attend briefings. 4 However, her interest in what political leaders from previous administrations have to say shows that she is also interested in earlier decisions that left the UK weakened, contrary to an independent assessment that suggested that it was well prepared.
A Novel Group of Dynamin-Related Proteins Shared by Eukaryotes and Giant Viruses Is Able to Remodel Mitochondria From Within the Matrix
Authors: Shaghayegh Sheikh, Tomáš Pánek, Ondřej Gahura, Jiří Týč, Kristína Záhonová, Julius Lukeš, Marek Eliáš, Hassan Hashimi
Journal: Molecular Biology and Evolution (2023)

Abstract The diverse GTPases of the dynamin superfamily play various roles in the cell, as exemplified by the dynamin-related proteins (DRPs) Mgm1 and Opa1, which remodel the mitochondrial inner membrane in fungi and metazoans, respectively. Via an exhaustive search of genomic and metagenomic databases, we found previously unknown DRP types occurring in diverse eukaryotes and giant viruses (phylum Nucleocytoviricota). One novel DRP clade, termed MidX, combined hitherto uncharacterized proteins from giant viruses and six distantly related eukaryote taxa (Stramenopiles, Telonemia, Picozoa, Amoebozoa, Apusomonadida, and Choanoflagellata). MidX stood out because it was not only predicted to be mitochondria-targeted but also to assume a tertiary structure not observed in other DRPs before. To understand how MidX affects mitochondria, we exogenously expressed MidX from Hyperionvirus in the kinetoplastid Trypanosoma brucei, which lacks Mgm1 or Opa1 orthologs. MidX massively affected mitochondrial morphology from inside the matrix, where it closely associates with the inner membrane. This unprecedented mode of action contrasts to those of Mgm1 and Opa1, which mediate inner membrane remodeling in the intermembrane space. We speculate that MidX was acquired in Nucleocytoviricota evolution by horizontal gene transfer from eukaryotes and is used by giant viruses to remodel host mitochondria during infection. MidX's unique structure may be an adaptation for reshaping mitochondria from the inside. Finally, Mgm1 forms a sister group to MidX and not Opa1 in our phylogenetic analysis, throwing into question the long-presumed homology of these DRPs with similar roles in sister lineages.
Asthma symptoms, spirometry and air pollution exposure in schoolchildren in an informal settlement and an affluent area of Nairobi, Kenya
Authors: Hellen Meme, Evans Amukoye, Cressida Bowyer, Jeremiah Chakaya, Darpan Das, Ruaraidh Dobson, Ulrike Dragosits, Jonathan Fuld, Cindy Gray, Matthew Hahn, Richard Kiplimo, Maia Lesosky, Miranda M Loh, Jean McKendree, Kevin Mortimer, Amos Ndombi, Louis Netter, Angela Obasi, Fred Orina, Clare Pearson, Heather Price, Jennifer K Quint, Sean Semple, Marsailidh Twigg, Charlotte Waelde, Anna Walnycki, Melaneia Warwick, Jana Wendler, Sarah E West, Michael Wilson, Lindsay Zurba, Graham Devereux
Journal: Thorax (2023)

Background Although 1 billion people live in informal (slum) settlements, the consequences for respiratory health of living in these settlements remain largely unknown. This study investigated whether children living in an informal settlement in Nairobi, Kenya are at increased risk of asthma symptoms. Methods Children attending schools in Mukuru (an informal settlement in Nairobi) and a more affluent area (Buruburu) were compared. Questionnaires quantified respiratory symptoms and environmental exposures; spirometry was performed; personal exposure to particulate matter (PM 2.5 ) was estimated. Results 2373 children participated, 1277 in Mukuru (median age, IQR 11, 9–13 years, 53% girls), and 1096 in Buruburu (10, 8–12 years, 52% girls). Mukuru schoolchildren were from less affluent homes, had greater exposure to pollution sources and PM 2.5 . When compared with Buruburu schoolchildren, Mukuru schoolchildren had a greater prevalence of symptoms, ‘current wheeze’ (9.5% vs 6.4%, p=0.007) and ‘trouble breathing’ (16.3% vs 12.6%, p=0.01), and these symptoms were more severe and problematic. Diagnosed asthma was more common in Buruburu (2.8% vs 1.2%, p=0.004). Spirometry did not differ between Mukuru and Buruburu. Regardless of community, significant adverse associations were observed with self-reported exposure to ‘vapours, dusts, gases, fumes’, mosquito coil burning, adult smoker(s) in the home, refuse burning near homes and residential proximity to roads. Conclusion Children living in informal settlements are more likely to develop wheezing symptoms consistent with asthma that are more severe but less likely to be diagnosed as asthma. Self-reported but not objectively measured air pollution exposure was associated with increased risk of asthma symptoms.
Evidence-Based De-Escalation in Axillary Management—Is Less Really More?
Authors: Leisha C. Elmore, Steven G. Woodward, Oluwadamilola M. Fayanju
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Cross-Sectional Analysis of Insurance Coverage for Lymphedema Treatments in the United States
Authors: Jeremy V. Lynn, Geoffrey E. Hespe, Maheen F. Akhter, Christelle M. David, Theodore A. Kung, Paige L. Myers
Journal: JAMA Surgery (2023)

Importance Lymphedema is a debilitating condition that affects approximately 1 in 1000 individuals in the United States. Complete decongestive therapy is currently the standard of care, and innovative surgical techniques have demonstrated potential to further improve outcomes. Despite the growing armamentarium of treatment options, a large proportion of patients with lymphedema continue to struggle because of limited access to care. Objective To define the current state of insurance coverage for lymphedema treatments in the United States. Design, Setting, and Participants A cross-sectional analysis of insurance reimbursement for lymphedema treatments in 2022 was designed. The top 3 insurance companies per state based on market share and enrollment data maintained by the Kaiser Family Foundation were included. Established medical policies were gathered from insurance company websites and phone interviews, and descriptive statistics were performed. Main Outcomes and Measures Treatments of interest included nonprogrammable pneumatic compression, programmable pneumatic compression, surgical debulking, and physiologic procedures. Primary outcomes included level of coverage and criteria for coverage. Results This study included 67 health insurance companies representing 88.7% of the US market share. Most insurance companies offered coverage for nonprogrammable (n = 55, 82.1%) and programmable (n = 53, 79.1%) pneumatic compression. However, few insurance companies offered coverage for debulking (n = 13, 19.4%) or physiologic (n = 5, 7.5%) procedures. Geographically, the lowest rates of coverage were seen in the West, Southwest, and Southeast. Conclusions and Relevance This study suggests that in the United States, less than 12% of individuals with health insurance, and even fewer patients without health insurance, have access to pneumatic compression and surgical treatments for lymphedema. The stark inadequacy of insurance coverage must be addressed through research and lobbying efforts to mitigate health disparities and promote health equity among patients with lymphedema.
Enhancement of CAR‐T cell activity against cholangiocarcinoma by simultaneous knockdown of six inhibitory membrane proteins
Authors: Yidan Qiao, Jie Chen, Xuemei Wang, Shumei Yan, Jizhou Tan, Baijin Xia, Yongjian Chen, Keming Lin, Fan Zou, Bingfeng Liu, Xin He, Yiwen Zhang, Xu Zhang, Hui Zhang, Xiangyuan Wu, Lijuan Lu
Journal: Cancer Communications (2023)

Abstract Background Existing treatments for cholangiocarcinoma have poor efficacy. However, chimeric antigen receptor‐T (CAR‐T) cells are emerging as a potential therapeutic strategy. Solid tumors possess multiple adverse factors in an immunosuppressive microenvironment that impair CAR‐T cell infiltration and function. This study aimed to improve the function of CAR‐T cells through knock down immune checkpoints and immunosuppressive molecular receptors. Methods We evaluated the expression of epidermal growth factor receptor (EGFR) and B7 homolog 3 protein (B7H3) antigens in cholangiocarcinoma tissues using immunohistochemistry and screened specific immune checkpoints in the cholangiocarcinoma microenvironment via flow cytometry. Subsequently, we engineered CAR‐T cells targeting EGFR and B7H3 antigens. We simultaneously knocked down immune checkpoints and immunosuppressive molecular receptors in CAR‐T cells by constructing two clusters of small hairpin RNAs and evaluated the engineered CAR‐T cells for antitumor activity both in vitro, using tumor cell lines and cholangiocarcinoma organoid models, and in vivo, using humanized mouse models. Results We observed high expression of EGFR and B7H3 antigens in cholangiocarcinoma tissues. EGFR‐CAR‐T and B7H3‐CAR‐T cells demonstrated specific anti‐tumor activity. We found an abundance of programmed cell death protein 1 (PD‐1), T cell immunoglobulin and mucin domain‐containing protein 3 (Tim‐3), and T cell immunoglobulin and ITIM domain (Tigit) on infiltrated CD8 + T cells in the cholangiocarcinoma microenvironment. We then decreased the expression of these 3 proteins on the surface of CAR‐T cells, named PTG‐scFV‐CAR‐T cells. Furthermore, we knocked‐down the expression of transforming growth factor beta receptor (TGFβR), interleukin‐10 receptor (IL‐10R), and interleukin‐6 receptor (IL‐6R) of PTG‐scFV‐CAR‐T cells. Those cells, named PTG‐T16R‐scFV‐CAR‐T cells, potently killed tumor cells in vitro and promoted apoptosis of tumor cells in a cholangiocarcinoma organoid model. Finally, the PTG‐T16R‐scFv‐CAR‐T cells showed greater inhibitory effect on tumor growth in vivo, and were superior in prolonging the survival of mice. Conclusions Our results revealed that PTG‐T16R‐scFV‐CAR‐T cells with knockdown of sextuplet inhibitory molecules exhibited strong immunity against cholangiocarcinoma and long‐term efficacy both in vitro and in vivo. This strategy provides an effective and personalized immune cell therapy against cholangiocarcinoma.
Transformative Materials for Interfacial Drug Delivery
Authors: Prachi Desai, Anshuman Dasgupta, Alexandros Marios Sofias, Quim Peña, Robert Göstl, Ioana Slabu, Ulrich Schwaneberg, Thomas Stiehl, Wolfgang Wagner, Stefan Jockenhövel, Julia Stingl, Rafael Kramann, Christian Trautwein, Tim H. Brümmendorf, Fabian Kiessling, Andreas Herrmann, Twan Lammers
Journal: Advanced Healthcare Materials (2023)

Abstract Drug delivery systems (DDS) are designed to temporally and spatially control drug availability and activity. They assist in improving the balance between on‐target therapeutic efficacy and off‐target toxic side effects. DDS aid in overcoming biological barriers encountered by drug molecules upon applying them via various routes of administration. They are furthermore increasingly explored for modulating the interface between implanted (bio)medical materials and host tissue. Herein, an overview of the biological barriers and host‐material interfaces encountered by DDS upon oral, intravenous, and local administration is provided, and material engineering advances at different time and space scales to exemplify how current and future DDS can contribute to improved disease treatment are highlighted.
Using Artificial Intelligence to Assess Surgeon Skill
Authors: James Wu, O. Joe Hines
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Decreased miR-451a in cerebrospinal fluid, a marker for both cognitive impairment and depressive symptoms in Alzheimer's disease
Authors: Hu Feng, Panpan Hu, Yan Chen, Huaiqing Sun, Jiachen Cai, Xiaoxin He, Qiuchen Cao, Mengmei Yin, Yanli Zhang, Qian Li, Junying Gao, Charles Marshall, Chengyu Sheng, Jingping Shi, Ming Xiao
Journal: Theranostics (2023)

Background: Alzheimer's disease (AD) patients are often accompanied by depressive symptoms, but its underlying mechanism remains unclear.The present study aimed to explore the potential role of microRNAs in the comorbidity of AD and depression.Methods: The miRNAs associated with AD and depression were screened from databases and literature and then confirmed in the cerebrospinal fluid (CSF) of AD patients and different ages of transgenic APP/PS1 mice.AAV9-miR-451a-GFP was injected into the medial prefrontal cortex (mPFC) of APP/PS1 mice at seven months, and four weeks later, a series of behavioral and pathological analyses were performed.Results: AD patients had low CSF levels of miR-451a, which was positively correlated with the cognitive assessment score, but negatively with their depression scale.In the mPFC of APP/PS1 transgenic mice, the miR-451a levels also decreased significantly in the neurons and microglia.Specific virus vector-induced overexpression of miR-451a in the mPFC of APP/PS1 mice ameliorated AD-related behavior deficits and pathologies, including long-term memory defects, depression-like phenotype, β-amyloid load, and neuroinflammation.Mechanistically, miR-451a decreased the expression of neuronal β-secretase 1 of neurons through inhibiting Toll-like receptor 4/Inhibitor of kappa B Kinase β/ Nuclear factor kappa-B signaling pathway and microglial activation by inhibiting activation of NOD-like receptor protein 3, respectively.Conclusion: This finding highlighted miR-451a as a potential target for diagnosing and treating AD, especially for those with coexisting symptoms of depression.